Serum metabolomic profiling of incident type 2 diabetes mellitus in the Multi-Ethnic Study of Atherosclerosis and Rotterdam Study.

Objective: This study aimed to investigate serum metabolomic biomarkers associated with incident type 2 diabetes mellitus (T2DM) and evaluate their performance in improving T2DM risk prediction.

Methods: Untargeted proton nuclear magnetic resonance (1H NMR) spectroscopy-based metabolomics analyses were conducted in the Multi-Ethnic Study of Atherosclerosis (MESA; n=3460; discovery cohort) and Rotterdam Study (RS; n=1556; replication cohort). Multivariable cause-specific hazards models were used to analyze the associations between 23,571 serum metabolomic spectral variables and incident T2DM.

Feasibility of remote monitoring for fatal coronary heart disease using Apple Watch ECGs.

Background: Fatal coronary heart disease (FCHD) is often described as sudden cardiac death (affects >4 million people/year), where coronary artery disease is the only identified condition. Electrocardiographic artificial intelligence (ECG-AI) models for FCHD risk prediction using ECG data from wearable devices could enable wider screening/monitoring efforts.

Objectives: To develop a single-lead ECG-based deep learning model for FCHD risk prediction and assess concordance between clinical and Apple Watch ECGs.

LXR signaling pathways link cholesterol metabolism with risk for prediabetes and diabetes.

BACKGROUNDPreclinical studies suggest that cholesterol accumulation leads to insulin resistance. We previously reported that alterations in a monocyte cholesterol metabolism transcriptional network (CMTN) - suggestive of cellular cholesterol accumulation - were cross-sectionally associated with obesity and type 2 diabetes (T2D). Here, we sought to determine whether the CMTN alterations independently predict incident prediabetes/T2D risk, and correlate with cellular cholesterol accumulation.

CLINICAL HETEROGENEITY IN THE AGE OF BIG DATA, ADVANCED ANALYTICS, AND COMPLEXITY THEORY.

Clinical heterogeneity remains a challenge in the practice of medicine and is an underlying motivation for much of biomedical research. Unfortunately, despite an abundance of technologies capable of producing millions of discrete data elements with information about a patient's health status or disease prognosis, our ability to translate those data into meaningful improvements in understanding of clinical heterogeneity is limited. To address this gap, we have applied newer approaches to manifold learning and developed additional and complementary techniques to interrogate and interpret complex, high dimensional omics data.

Statins and Left Ventricular Ejection Fraction Following Doxorubicin Treatment.

Background: Statins taken for cardiovascular indications by patients with breast cancer and lymphoma during doxorubicin treatment may attenuate left ventricular ejection fraction (LVEF) decline, but the effect of statins on LVEF among patients with no cardiovascular indications is unknown.

Methods: A double-blind, placebo-controlled, 24-month randomized trial of 40 mg of atorvastatin per day administered to patients with breast cancer and lymphoma receiving doxorubicin was conducted within the National Cancer Institute Community Oncology Research Program across 31 sites in the United States. At pretreatment and then 6 and 24 months after initiating doxorubicin, we assessed left ventricular (LV) volumes, strain, mass, and LVEF through cardiac magnetic resonance imaging, along with cognitive function and serum markers of inflammation.

Venous or arterial thrombosis in COVID-19 cases in the North Carolina COVID-19 Community Research Partnership (NC-CCRP).

Background: Although the incidence of venous and arterial thrombosis after a COVID-19 diagnosis and hospitalization has been well described using data available from electronic health records (EHR), little is known about their incidence after mild infections.

Objectives: To characterize the cumulative incidence and risk factors for thrombosis after a COVID-19 diagnosis among those identified through the EHR and those with a self-reported case.

Methods: We calculated the cumulative incidence of thromboembolism diagnoses after EHR-identified and self-reported cases in the North Carolina COVID-19 Community Partnership, a prospective, multisite, longitudinal surveillance cohort using a Kaplan-Meier approach.

COVID-19 Symptoms by Variant Period in the North Carolina COVID-19 Community Research Partnership, North Carolina, USA.

In North Carolina, USA, the SARS-CoV-2 Omicron variant was associated with changing symptomology in daily surveys, including increasing rates of self-reported cough and sore throat and decreased rates of loss of taste and smell. Compared with the pre-Delta period, Delta and Omicron (pre-BA.4/BA.

Breakthrough SARS-CoV-2 Infections after Vaccination in North Carolina.

We characterize the overall incidence and risk factors for breakthrough infection among fully vaccinated participants in the North Carolina COVID-19 Community Research Partnership cohort. Among 15,808 eligible participants, 638 reported a positive SARS-CoV-2 test after vaccination. Factors associated with a lower risk of breakthrough in the time-to-event analysis included older age, prior SARS-CovV-2 infection, higher rates of face mask use, and receipt of a booster vaccination.

Relationship of low-density lipoprotein-cholesterol and lipoprotein(a) to cardiovascular risk: The Multi-Ethnic Study of Atherosclerosis (MESA).

Background And Aims: Plasma low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) (Lp(a)) are both associated with coronary heart disease (CHD). This study investigated whether elevated plasma Lp(a) concentration was associated with increased CHD risk when LDL-C was low (≤100 mg/dL) in individuals not on statin therapy.

Methods: Participants from the Multi-Ethnic Study of Atherosclerosis (MESA) (n = 4,585) were categorized into four groups: Group 1: LDL-C ≤ 100 mg/dL, Lp(a) < 50 mg/dL; Group 2: LDL-C > 100 mg/dL, Lp(a) < 50 mg/dL; Group 3: LDL-C ≤ 100 mg/dL, Lp(a) ≥ 50 mg/dL; and Group 4: LDL-C > 100 mg/dL, Lp(a) ≥ 50 mg/dL.

Eicosapentaenoic Acid Ameliorates Cardiac Fibrosis and Tissue Inflammation in Spontaneously Hypertensive Rats.

Hypertension affects 1 in 3 adults in the United States and leads to left ventricular (LV) concentric hypertrophy, interstitial fibrosis, and increased stiffness. The treatment of cardiac fibrosis remains challenging and empiric. Eicosapentaenoic acid (EPA) is an omega-3 polyunsaturated fatty acid that is highly effective in reducing cardiovascular events in patients and cardiac fibrosis and hypertrophy in animals when administered before pressure overload by promoting the increase of anti-inflammatory M1 macrophages.

Vaccine-induced seroconversion in participants in the North Carolina COVID-19 community Research Partnership.

Well-regulated clinical trials have shown FDA-approved COVID-19 vaccines to be immunogenic and highly efficacious. We evaluated seroconversion rates in adults reporting ≥ 1 dose of an mRNA COVID-19 vaccine in a cohort study of nearly 8000 adults residing in North Carolina to validate immunogenicity using a novel approach: at-home, participant administered point-of-care testing. Overall, 91.

Frailty and COVID-19 mRNA Vaccine Antibody Response in the COVID-19 Community Research Partnership.

Background: COVID-19 has disproportionately affected older adults. Frailty has been associated with impaired vaccine response in other vaccine types, but the impact of frailty on mRNA vaccine response is undefined.

Methods: Observational study of adults aged 55 and older from 1 U.

Finding Correspondence between Metabolomic Features in Untargeted Liquid Chromatography-Mass Spectrometry Metabolomics Datasets.

Integration of multiple datasets can greatly enhance bioanalytical studies, for example, by increasing power to discover and validate biomarkers. In liquid chromatography-mass spectrometry (LC-MS) metabolomics, it is especially hard to combine untargeted datasets since the majority of metabolomic features are not annotated and thus cannot be matched by chemical identity. Typically, the information available for each feature is retention time (RT), mass-to-charge ratio (/), and feature intensity (FI).

Analysis of accumulated SARS-CoV-2 seroconversion in North Carolina: The COVID-19 Community Research Partnership.

Introduction: The COVID-19 Community Research Partnership is a population-based longitudinal syndromic and sero-surveillance study. The study includes over 17,000 participants from six healthcare systems in North Carolina who submitted over 49,000 serology results. The purpose of this study is to use these serology data to estimate the cumulative proportion of the North Carolina population that has either been infected with SARS-CoV-2 or developed a measurable humoral response to vaccination.

Automated Annotation of Untargeted All-Ion Fragmentation LC-MS Metabolomics Data with MetaboAnnotatoR.

Untargeted metabolomics and lipidomics LC-MS experiments produce complex datasets, usually containing tens of thousands of features from thousands of metabolites whose annotation requires additional MS/MS experiments and expert knowledge. All-ion fragmentation (AIF) LC-MS/MS acquisition provides fragmentation data at no additional experimental time cost. However, analysis of such datasets requires reconstruction of parent-fragment relationships and annotation of the resulting pseudo-MS/MS spectra.

Monocyte chemoattractant protein-1 is not predictive of cardiac events in patients with non-low-risk chest pain.

Background: Prior studies suggest monocyte chemoattractant protein-1 (MCP-1) may be useful for risk stratifying ED patients with chest pain. We hypothesise that MCP-1 will be predictive of 90-day major adverse cardiovascular events (MACEs) in non-low-risk patients.

Methods: A case-control study was nested within a prospective multicentre cohort (STOP-CP), which enrolled adult patients being evaluated for acute coronary syndrome at eight US EDs from 25 January 2017 to 06 September 2018.

Alcohol Consumption and Systemic Hypertension (from the Third National Health and Nutrition Examination Survey).

Epidemiological studies have established the association between excessive alcohol consumption and systemic hypertension (SH). However, there are conflicting reports of the association of low to moderate alcohol consumption with SH. The objective of the study was to examine the associations of alcohol consumption and blood pressure categories using the 2017 American College of Cardiology/American Heart Association high blood pressure guidelines.

High-Sensitivity C-Reactive Protein Modifies the Cardiovascular Risk of Lipoprotein(a): Multi-Ethnic Study of Atherosclerosis.

Background: Little is known about the relationship between lipoprotein (a) [Lp(a)] and high-sensitivity C-reactive protein (hsCRP) and their joint association with atherosclerotic cardiovascular disease (ASCVD).

Objectives: The purpose of this study was to assess whether Lp(a)-associated ASCVD risk is modified by hsCRP in the context of primary prevention.

Methods: The current study included 4,679 participants from the MESA (Multi-Ethnic Study of Atherosclerosis) Apolipoprotein ancillary data set.

Changing Attitudes toward the COVID-19 Vaccine among North Carolina Participants in the COVID-19 Community Research Partnership.

Coronavirus Disease-2019 (COVID-19) vaccine acceptance is variable. We surveyed participants in the COVID-19 Community Research Partnership from 17 December 2020 to 13 January 2021 to assess vaccine receptiveness. Vaccine uptake was then monitored until 15 May 2021; 20,232 participants responded to the receptiveness survey with vaccination status accessed in 18,874 participants via daily follow-up surveys (participants not completing daily surveys ≥30 days to 15 May 2021, were excluded).

Associations of circulating choline and its related metabolites with cardiometabolic biomarkers: an international pooled analysis.

Background: Choline is an essential nutrient; however, the associations of choline and its related metabolites with cardiometabolic risk remain unclear.

Objective: We examined the associations of circulating choline, betaine, carnitine, and dimethylglycine (DMG) with cardiometabolic biomarkers and their potential dietary and nondietary determinants.

Methods: The cross-sectional analyses included 32,853 participants from 17 studies, who were free of cancer, cardiovascular diseases, chronic kidney diseases, and inflammatory bowel disease.

Circulating trimethylamine N-oxide in association with diet and cardiometabolic biomarkers: an international pooled analysis.

Background: Trimethylamine N-oxide (TMAO), a diet-derived, gut microbial-host cometabolite, has been linked to cardiometabolic diseases. However, the relations remain unclear between diet, TMAO, and cardiometabolic health in general populations from different regions and ethnicities.

Objectives: To examine associations of circulating TMAO with dietary and cardiometabolic factors in a pooled analysis of 16 population-based studies from the United States, Europe, and Asia.

Chronic Ca/Calmodulin-Dependent Protein Kinase II Inhibition Rescues Advanced Heart Failure.

Ca/calmodulin-dependent protein kinase II (CaMKII) is upregulated in congestive heart failure (CHF), contributing to electrical, structural, and functional remodeling. CaMKII inhibition is known to improve CHF, but its direct cardiac effects in CHF remain unclear. We hypothesized that CaMKII inhibition improves cardiomyocyte function, [Ca] regulation, and -adrenergic reserve, thus improving advanced CHF.

Comparison of the Relation of Carotid Intima-Media Thickness With Incident Heart Failure With Reduced Versus Preserved Ejection Fraction (from the Multi-Ethnic Study of Atherosclerosis [MESA]).

Increased carotid intima-media thickness (cIMT) is associated with heart failure (HF) in previous studies, but it is not known whether the association of cIMT differs between HF with reduced (HFrEF) versus preserved ejection fraction (HFpEF). We studied 6699 participants (mean age 62 ± 10 years, 47% male, and 38% white) from the Multi-Ethnic Study of Atherosclerosis (MESA) with baseline cIMT measurements. We classified HF events as HFrEF (EF <50%) or HFpEF (EF ≥ 50%) at the time of diagnosis.

Sex and race differences in safety and effectiveness of the HEART pathway accelerated diagnostic protocol for acute chest pain.

Background: The HEART Pathway is an accelerated diagnostic protocol for Emergency Department patients with possible acute coronary syndrome. The objective was to compare the safety and effectiveness of the HEART Pathway among women vs men and whites vs non-whites.

Methods: A subgroup analysis of the HEART Pathway Implementation Study was conducted.